Galactorrhea Due to Hypothyroidism Case File
Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD
CASE 50
A 30-year-old parous woman notes a watery breast discharge of 6 months’ duration. Her menses have been somewhat irregular. She denies a family history of breast cancer. The patient had been treated previously with radioactive iodine for Graves disease. Currently, she is not taking any medications. On examination, she appears alert and in good health. The blood pressure is 120/80 mm Hg, and heart rate is 80 beats per minute. The breasts are symmetric and without masses. No skin retraction is noted. A white discharge can be expressed from both breasts. No adenopathy is appreciated. The pregnancy test is negative.
» What is the most likely diagnosis?
» What is your next step?
» What is the likely mechanism for this disorder?
ANSWER TO CASE 50:
Galactorrhea Due to Hypothyroidism
Summary: A 30-year-old parous woman with irregular menses notes a watery breast discharge of 6 months’ duration. She had been treated previously with radioactive iodine for Graves disease. The pregnancy test is negative.
- Most likely diagnosis: Galactorrhea due to hypothyroidism.
- Next step: Check serum prolactin and thyroid-stimulating hormone (TSH) levels.
- Likely mechanism: Hypothyroidism is associated with an elevated thyroidreleasing hormone (TRH) level, which acts as a prolactin-releasing hormone. The hyperprolactinemia then induces the galactorrhea.
ANALYSIS
Objectives
- Know the clinical presentation of galactorrhea.
- Know some of the major causes of hyperprolactinemia.
- Understand that hyperprolactinemia can induce hypothalamic dysfunction leading to oligo-ovulation and irregular menses.
Considerations
This patient complains of oligomenorrhea and a white, watery breast discharge, which is likely to be milk (galactorrhea). The first investigation should be a pregnancy test. Causes of galactorrhea include a pituitary adenoma, pregnancy, breast stimulation, medications, chest wall trauma, or hypothyroidism. She does not have headaches or visual disturbances. This woman had been treated previously with radioactive iodine for Graves disease and is not taking thyroid replacement. Thus, she likely has hypothyroidism. With primary hypothyroidism, both the thyroid-releasing hormone and thyroid-stimulating hormone are elevated. TRH acts as a prolactin-releasing hormone. Hence, elevated TSH and prolactin levels will be noted in this patient. Hyperprolactinemia results in a reflex increase in dopamine in the brain. Dopamine stimulates receptors on cells of the hypothalamus that produce GnRH interrupting its pulsatile release. Thus, gonadotropin release is inhibited. In turn, follicle development is disrupted, estradiol decreases, and menstrual cycles become irregular or cease. This patient would have no bleeding in response to a progestin challenge test due to insufficient endometrium. (See Case 49, Intrauterine adhesions.)
APPROACH TO:
Galactorrhea
DEFINITIONS
GALACTORRHEA: Nonpuerperal watery or milky breast secretion that contains neither pus nor blood. The secretion can be manifested spontaneously or obtained only by breast examination.
PITUITARY SECRETING ADENOMA: A tumor in the pituitary gland that produces prolactin; symptoms include galactorrhea, headache, and peripheral vision defect (bitemporalhemianopsia).
CLINICAL APPROACH
Galactorrhea is a milky breast secretion that occurs in a nonlactating patient. It is usually bilateral. To determine if the breast discharge is truly galactorrhea, a smear under microscope will reveal multiple fat droplets. Patients with galactorrhea often have associated oligomenorrhea or amenorrhea. See Table 50– 1 for the different etiologies for hyperprolactinemia.
Galactorrhea and hyperprolactinemia require a careful diagnostic approach. A thorough history and physical should be done. All medications that can stimulate prolactin production should be discontinued. A magnetic resonance scan is the most sensitive test to detect pituitary adenomas, providing 1-mm resolution; it can detect virtually all microadenomas. Prolactin should be evaluated in the morning when it is at its lowest physiological level. Nonpregnant prolactin is less than 20 ng/mL. Microadenomas are <10 mm diameter; macroadenomas are >10 mm. Macroadenomas of any cell type, not merely prolactinomas, should be imaged by magnetic resonance(MRI) because macroadenomas can damage the pituitary stalk and thereby decrease the normal dopamine inhibition of pituitary lactotropes. MRI is performed with and without gadolinium. Those with a markedly high prolactin level, or those with neurologic symptoms, should have an MRI of the pituitary. Hyperprolactinemia is a common cause of menstrual disturbances. Hence, a woman with galactorrhea, regular menses, and normal serum prolactin is at low risk for having a prolactinoma. These patients can be followed with annual serum prolactin tests.
However, even in the face of normal prolactin assays, women with oligomenorrhea and galactorrhea should undergo an anteroposterior and lateral coned-down view of the sellaturcica. If necessary, a skull MRI will confirm the diagnosis of empty sella. Patients with secondary amenorrhea and low levels of serum estrogen (< 40 pg/mL) have a significantly greater risk of having a pituitary adenoma as well as early onset of osteoporosis.
Women with galactorrhea but normal menses and normal serum prolactin levels may be observed. Also, patients with microadenomas who do not wish to conceive and do not have estrogen deficiency may be expectantly managed. Other patients with pituitary adenomas should receive treatment, which is primarily medical management and rarely surgical.
If the hyperprolactinemia is found to be due to hypothyroidism, the patient should be treated with thyroxine. Symptomatic patients with hyperprolactinemia due to a pituitary microadenoma or asymptomatic patients with a macroadenoma should be treated with a dopamine agonist, such as bromocriptine, a nonselective dopamine receptor agonist. Its side effects (orthostatic hypotension, fainting, dizziness, and nausea and vomiting). Bromocriptine is particularly useful for patients desiring fertility. Cabergoline is a selective type 2 dopamine receptor agonist for patients and has less side effects and lowers prolactin levels more effectively; it is also available in depot form. Both bromocriptine and cabergoline can be given vaginally if the patient does not tolerate the oral form. Patients with hyperprolactinemia, with or without microadenoma, with adequate estrogen levels (> 40 pg/mL) and who do not desire pregnancy should be treated with periodic progestin withdrawal.
Patients who fail medical therapy may require surgery, which involves transsphenoidal microsurgical exploration of the sellaturcica with removal of the pituitary adenoma while preserving the functional capacity of the remaining gland. Complications of the surgery include transient diabetes insipidus (occurs in about one-third), hemorrhage, meningitis, cerebrospinal fluid leak, and panhypopituitarism. Cure rate is directly related to the pretreatment prolactin levels (prolactin level of 100 ng/ mL has an excellent prognosis, whereas 200 ng/ mL has a poor prognosis). It may be preferable to reduce the size of the macroadenoma with bromocriptine before surgical removal of these tumors.
|
CASE CORRELATION
|
COMPREHENSION QUESTIONS
50.1 A 25-year-old woman presents with galactorrhea and irregular menses of 10 months’ duration. Her pregnancy test is negative. Laboratory tests reveal normal TSH and serum-free T4 and hyperprolactinemia. Which of the following is most likely to be a cause of her condition?
A. Posterior pituitary adenomaB. Abdominal wall traumaC. Psychotropic medicationD. Hyperthyroidism
50.2 A 38-year-old woman is seen by her physician because of headaches, amenorrhea, and galactorrhea. Her pregnancy test was negative. Her prolactin level was markedly elevated and TSH was normal. The physician makes a presumptive diagnosis of pituitary adenoma and orders an MRI of the brain. Which of the following clinical presentations is consistent with a prolactinsecreting pituitary adenoma?
A. Diabetes insipidusB. Occipital cerebral defectC. Central field visual defectD. Amenorrhea at the hypothalamus level
50.3 A 47-year-old woman is being evaluated for a possible pituitary tumor. She complains of headaches and has some visual difficulties. The MRI shows a mass in the posterior pituitary gland, which the radiologist notes is unusual. Which of the following is a hormone contained in the posterior pituitary gland?
A. Follicle-stimulating hormone (FSH)B. ProlactinC. Thyroid-stimulating hormoneD. Oxytocin
50.4 A 33-year-old woman with a microadenoma of the pituitary gland becomes pregnant. When she reaches 28 weeks’ gestation, she complains of headaches and visual disturbances. Which of the following is the best therapy?
A. Craniotomy and pituitary resectionB. Tamoxifen therapyC. Oral bromocriptine therapyD. Expectant managementE. Lumbar puncture
ANSWERS
50.1 C. Medications are a common cause of hyperprolactinemia, especially psychotropic medications. Pregnancy is associated with elevated prolactin levels. The anterior, not posterior, pituitary secretes prolactin; an anterior pituitary adenoma is more likely to be a cause of hyperprolactinemia. Symptoms may include galactorrhea, headache, and peripheral vision defect (bitemporalhemianopsia). Hypothyroidism may lead to hyperprolactinemia. With primary hypothyroidism, both TRH (secreted by the hypothalamus) and TSH (secreted by anterior pituitary) levels are elevated. TRH acts as a prolactinreleasing hormone in addition to being a thyroid-releasing hormone. Chest wall trauma, and not abdominal wall trauma, can cause hyperprolactinemia.
50.2 D. Elevated prolactin levels inhibit GnRH pulsations from the hypothalamus. Without the signal from GnRH, gonadotropins (FSH/ LH) are not released from the anterior pituitary and no estrogen (or progesterone) is released from the ovaries; this results in amenorrhea. Pituitary adenomas impinge on the optic chiasm, causing deficits of the peripheral vision (bitemporalhemianopsia) and not the central visual field. The pituitary is located in the anterior half of the cerebrum; therefore, an occipital cerebral defect is unlikely to be a clinical presentation relating to a pituitary adenoma. Diabetes insipidus results from a deficiency in antidiuretic hormone (ADH) from the posterior pituitary, and would not be a clinical presentation consistent with an anterior pituitary tumor.
50.3 D. Oxytocin and ADH are posterior pituitary hormones. The other answer choices are released by the anterior pituitary. Whereas prolactin acts on the breast to produce milk, oxytocin acts on the breast to stimulate ejection of the milk in a lactating woman. Oxytocin is also responsible for uterine contractions during labor. The main function of FSH is to stimulate follicular development and maturity in the ovaries. ADH acts on the kidney to conserve water and is released when the body is dehydrated. TSH causes release of thyroid hormones, T3 and T4, which are involved in essential metabolic processes throughout the body.
50.4 C. Bromocriptine therapy is indicated during pregnancy if symptoms (eg, headache or visual field abnormalities) arise. No studies have shown bromocriptine to be unsafe to the developing fetus. A craniotomy and pituitary resection is a very high-risk surgery. It is typically reserved for patients with a macroadenoma, who have failed medical treatment. Surgery would not be indicated for this patient who has a microadenoma and has not attempted medical therapy. Plus, any procedure that may induce hemorrhage in a patient would be considered risky in pregnancy. Tamoxifen is not indicated because it is a selective estrogen receptor modulator used in the treatment of breast cancer. It therefore binds to estrogen receptors to inhibit estrogen action, and does not affect the microadenoma or prolactin production and action. A lumbar puncture would not be an option for managing a prolactinoma, but might worsen the patient’s headache. Expectant management would not be a good option because a microadenoma can continue to grow during pregnancy from hormonal influences. Therefore, the patient’s symptoms would only worsen, and treatment should be initiated promptly.
CLINICAL PEARLS
|
» Galactorrhea in the face of normal menses and a normal prolactin level may be observed. The normal menses indicates normal hypothalamic function. » The first evaluation in a woman with oligomenorrhea and galactorrhea should be a pregnancy test. » Osteoporosis is a danger with hypoestrogenemia due to hyperprolactinemia. » Hypothyroidism can lead to hyperprolactinemia and galactorrhea. » Both hypothyroidism and hyperprolactinemia lead to hypothalamic (interfere with pulsatile GnRH) amenorrhea; this is a hypogonadotropic hypogonadism. » MRI is the most sensitive imaging test to assess pituitary adenomas. |
REFERENCES
Alexander CJ, Mathur R, Laufer LR, Aziz R. Amenorrhea, oligomenorrhea, and hyper-androgenic disorders. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 6th ed. Philadelphia, PA: Saunders; 2015:355-367.
Fritz M, Speroff L. Amenorrhea. In: Fritz M, Speroff L, eds. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2010.
Halvorson LM. Hypothalamic amenorrhea. In: Schorge J, Schaffer J, Halvorson LM, et al., eds. Williams Gynecology. 2nd ed. New York, NY: McGraw-Hill; 2012:400-439.
Lobo RA. Hyperprolactinemia, galactorrhea, and pituitary adenomas. In: Katz VL, Lentz GM, Lobo RA, Gersenson DM, eds. Comprehensive Gynecology. 6th ed. St. Louis, MO: Mosby-Year Book; 2012:963-978.
0 comments:
Post a Comment
Note: Only a member of this blog may post a comment.